How Close Are We to Wearable Dialysis?

The concept of a wearable artificial kidney (WAK) is very good and promising work. Sorbent technology is likely the direction of future non-transplant renal replacement therapies. In the United States, the FDA has chosen it as a fast-track area for research and development. They have a good team on the case...all that and more, but in my view, it still has a long way to go yet before it reaches any form of commercial reality. While there are plans for further human testing as a follow-up to the small pilot study of 8 patients reported in the Lancet,¹ the status remains just that – testing.

There are challenges galore ahead to solve, including:

• The sorbents. Sorbents are materials that absorb (soak up) pretty much anything from the spent dialysate after it exits the dialyzer. By circulating the spent fluid through a column of different sorbents, the filtered waste can be removed, thus re-making the dialysate into a sterile mix of water, sodium chloride, and bicarbonate. The fluid is then ready for reconstitution as fresh dialysate by adding electrolytes such as calcium, potassium and magnesium for re-presentation to the dialyzer. Using sorbents allows the total dialysis fluid volume to be dramatically reduced. You may wish to read more about sorbents in a paper I wrote some time ago in Nephrology.²
• Connectology. This is a composite term I use here to encompass the vexed and problematic way blood must leave the body (via an access), be passaged through the dialysis system circuitry (the extracorporeal circuit), and then returned to the body (again, via an access).
• Anticoagulation. Anticoagulants are needed so blood doesn't clot in the circuit. The delivery of appropriate and regulated doses of anticoagulant to a miniaturized circuit presents some extra problems to overcome.
• Membrane size and format. A small, wearable system requires a small, wearable dialyzer. Traditional dialyzer membranes are 1.5-2.0 square metres – if rolled out flat. There are challenges to make a dialyser small enough to wear, yet big enough to provide adequate surface area for clearing waste and fluid. Nanotechnology is helping here, but significant challenges remain.
• Sustainable clearances and UF. Smaller filter membranes = a lesser surface area to permit fluid and waste removal. This is a significant hurdle to overcome – especially on a recurrent, day-after-day basis.
• Regulation of the system. Standard dialysis systems monitor stuff. They check transmembrane pressures, monitor conductivity (electrolyte concentrations), system temperature, air exclusion, pre and post dialyser pressures (arterial and venous pressure) and flow rates. Mastering all of these within a miniaturized system is not easy!
• Prevention of breakthrough. To my mind, this is a huge and unconquered limitation, especially in a small system. When used dialysis fluid is circulated through a sorbent column to absorb its' contained wastes and re-make it into a fluid ready for re-presentation to the dialyser for more waste extraction, the absorbing process can make "new" substances out of the old. The prime example = urea, which is converted to ammonium ions by a sorbent early on in the sorbent column. Ammonia is then absorbed further up the column by another, different layer of sorbent that captures and extracts ammonia. But, if this subsequent sorbent layer is overwhelmed, and becomes super-saturated...ammonia may escape beyond the ammonia-trapping layer and contaminate the exiting 're-made' dialysis fluid. While this can be detected, the consequences of ammonia ‘breakthrough' are significant. This presents a major challenge for all sorbent systems, whether large or miniaturized.
• Canister replacement, lifespan, and synchronization. The lifespan, the synchronization of the chain of required sorbents to ensure that the role of each sorbent is measured to the actions of the sorbent preceding it, and the mechanism and timing of canister replacement...all present problems to solve.
• Pump reliability. The system is driven by a battery-driven micro-pump – and this must be reliable and long-lasting.

All of these have a distance to go before a reliable system fully emerges. Thus far, the WAK has been an utterly amazing effort by Victor, whom I know well, to drive his 'love' this far, and almost single-handedly (with help and support from an equally amazing and very smart guy - Alan Davenport), both of whom rightfully have amazing faith in the concept.

The WAK is up against smaller and simpler desktop machines (some already in the pipeline), as well as smarter, targeted immunosuppressant drugs to improve transplantation. That said, I take my hat off to them. The lessons they will learn along the way will inform and advance miniaturization techniques and their incorporation into ever smaller iterations of systems like the Quanta SelfCare+ and the Physidia when their eventual Mark II and III versions appear. Either or both of these systems, while still RO dependent, may yet team with smarter, smaller, portable RO systems to provide full-on HD or, perhaps even better, HDF, in a truly portable package.

In fact, if it were me, I'd be whipping up the water boys to design a "pocket RO," or at least one that might fit into an overnight bag, using weight-reducing carbon fibre and smarter de-ionisation and nano-membrane technology...plus a home-clean system for re-charging and re-use. We really haven't chased that nearly hard enough!

But, the Achilles heel of all dialytic therapies remains access and extracorporeal circuit stability. This is perhaps especially so within the context of miniaturization—and even more especially when that miniaturization is extracorporeal.

As for implantability, other than the implantation of a transplanted kidney, in my view this still remains the stuff of science fiction—though the Dutch have toyed with this possibility. Many have thought long and hard about ways to solve access... this hardest of all problems...but the blood-to-exterior interface still beats us every time!

References

1. Davenport A et al. A wearable haemodialysis device for patients with end-stage renal failure: a pilot study. The Lancet. 2007. 370(9604) 2005-10
2. Agar JWM. Understanding Sorbent Dialysis Systems. Nephrology. 2010. 15(4):406-411.